Prostate cancer accounts for 122,000 new cases and 30,000 cancer-related deaths in the United States each year. Although hormone therapy is effective in approximately 70% of the men with metastatic cancer, ultimately they all suffer progressive disease with androgen-independent prostate cancer. No effective therapy exists for androgen-independent prostate cancer. The antiparasitic drug, suramin, has antiproliferative effects in human carcinoma cells. Most recently, suramin has demonstrated activity in patients with prostate cancer. We have developed evidence that suramin rapidly inhibits cellular respiration and disrupts cellular energy balance in intact prostate cancer cells. Disruption of energy balance or respiration represents a possible antiproliferative mechanism in cancer cells, as is felt to be a primary mechanism for suramin's action in parasitic diseases. This proposed mechanism of action for suramin can explain the most prominently observed clinical toxicities of nephrotoxicity, adrenal toxicity, coagulopathy and demyelinating neuropathy. This proposal outlines our plan to use suramin as a model to target cellular energy metabolism in antineoplastic therapy. we have outlined an experimental plan to further delineate suramin's mechanism of action and use of this knowledge to search for other drugs synergistic to suramin. Finally, we plan to utilize our Phase I drug development program to apply this knowledge in clinical settings, starting with our ongoing Phase I trial of suramin.